AKAP9, a Regulator of Microtubule Dynamics, is Essential for Remodeling of the Blood‐Testis Barrier

Abstract

The blood‐testis barrier (BTB) is formed by tight, adherens and gap junctions between adjacent Sertoli cells of the seminiferous tubules. The BTB undergoes extensive remodeling during the seminiferous epithelial cycle of spermatogenesis to allow the transport of preleptotene spermatocytes from the basal compartment to the adluminal compartment for further development. The actin cytoskeleton serves unique structural and supporting roles in this process, but little is known about the role of microtubules and their regulators in BTB remodeling. The cAMP responsive scaffold protein AKAP9 has been shown to regulate microtubule dynamics. We demonstrate that conditional and inducible deletion of AKAP9 in mice after the initial formation of the BTB leads to infertility despite evidence of germ cell meiosis. AKAP9 deletion results in marked alterations in the integrity of microtubules in Sertoli cells, mislocalization of gap and tight junctional molecules at the BTB and a progressive loss of barrier integrity despite normal localization of F‐actin at the BTB. These changes were accompanied by an arrest of meiosis and spermiogenesis. Unexpectedly, barrier integrity and meiosis were restored in older AKAP9 deficient animals. Yet, significant defects in spermiogenesis persisted suggesting a role for AKAP9 in the transport of developing spermatids across the adluminal compartment during spermiogenesis. These results suggest that AKAP9 is critical for both dynamic restructuring of the BTB during the epithelial cycle and subsequent spermiogenesis.